CTHRC1 overexpression promotes cervical carcinoma progression by activating the Wnt/PCP signaling pathway

Zheng, Mei; Zhou, Qin; Liu, Xingguang; Wang, Chengze; Liu, Gangli

doi:10.3892/or.2019.6963

Cited by 19 publications

(21 citation statements)

References 26 publications

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“…It has been confirmed that CTHRC1 can activate the SRC and ERK signal cascades and upregulate the expression of MMP9, thus promoting the invasion of CRC cells (22). Overexpression of CTHRC1 has been found to promote the occurrence and development of cervical cancer by activating the Wnt/PCP oncogenic signaling pathway (57). CTHRC1 induces EMT changes and MMP expression through the PI3K/AKT/ERK/CREB signaling pathway to promote the invasiveness and metastasis of hepatocellular carcinoma (58).…”

Section: Discussionmentioning

confidence: 91%

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

et al. 2020

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Cyclovirobuxine D (CVB-D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB-D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB-D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB-D and further elucidate its molecular mechanism(s). DLD-1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB-D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB-D-treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB-D in vivo. It was identified that CVB-D inhibited the proliferation, migration, stemness, angiogenesis and epithelial-mesenchymal transition of CRC cells, and induced apoptosis and S-phase arrest. In addition, CVB-D significantly inhibited the growth of xenografts. It is notable that CVB-D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB-D exerted anticancer effects through the CTHRC1-AKT/ERK-Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB-D may offer a promising novel therapeutic approach for CRC treatment.

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Section: Discussionmentioning

confidence: 91%

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

et al. 2020

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“…Among those predicted signaling pathways, the PCP signaling axis was the top pathway judged by significant p value and activation status (activation z-score = 3.162, Figure 4 A). PCP signaling is one of the noncanonical Wnt signaling pathways of whose aberrant activation could lead to tumor migratory properties [ 15 , 16 , 17 , 18 ]. The distribution of up- and downregulated gene targets is shown in Figure 4 B.…”

Section: Resultsmentioning

confidence: 99%

Leptin Is Associated with Poor Clinical Outcomes and Promotes Clear Cell Renal Cell Carcinoma Progression

et al. 2021

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Emerging evidence has shown the oncogenic roles of leptin in modulating cancer progression in addition to its original roles. Analyses of transcriptomic data and patients’ clinical information have revealed leptin’s prognostic significance in renal cell carcinoma (RCC). However, its biological effects on RCC progression have not yet been explored. Clinical and transcriptomic data of a RCC cohort of 603 patients were retrieved from The Cancer Genome Atlas (TCGA) and analyzed to reveal the correlation of leptin with clinical outcomes and the hierarchical clustering of gene signatures based on leptin levels. In addition, cox univariate and multivariate regression analyses, cell migration upon leptin treatment, identification of putative leptin-regulated canonical pathways via ingenuity pathway analysis (IPA), and the investigation of induction of Wnt5a, ROR2, and Jun N-terminal Kinases (JNK) phosphorylation activation were performed. We first observed a correlation of high leptin levels and poor outcomes in RCC patients. Knowledge-based analysis by IPA indicated the induction of cancer cell migration by leptin, which was manifested via direct leptin treatment in the RCC cell lines. In RCC patients with high leptin levels, the planar cell polarity (PCP)/JNK signaling pathway was shown to be activated, and genes in the axis, including CTHRC1, FZD2, FZD10, ROR2, WNT2, WNT4, WNT10B, WNT5A, WNT5B, and WNT7B, were upregulated. All of these genes were associated with unfavorable clinical outcomes. WNT5A and ROR2 are pivotal upstream regulators of PCP/JNK signaling, and their correlations with leptin expression levels were displayed by a Pearson correlation analysis. The inhibition of signal transduction by SP600125 reversed leptin-mediated cell migration properties in RCC cell lines. The results indicate the prognostic impact of leptin on RCC patients and uncover its ability to promote cell migration via PCP/JNK signaling.

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“…CTHRC1 played a role in the cellular response to arterial injury through involvement in vascular remodeling (Pyagay et al, 2005). Previous studies showed that CTHRC1 promoted tumor cell progression and might play a key role in the invasion metastasis of cervical carcinoma, cervical squamous cell carcinoma, and colorectal cancer (Ni et al, 2018;Li N. et al, 2019;Zheng et al, 2019). In addition, CTHRC1 promoted M2-like macrophage recruitment and myometrial invasion in endometrial carcinoma by the integrin-Akt signaling pathway, which indicated that CTHRC1 might be a biomarker for tumor immunotherapy .…”

Section: Discussionmentioning

confidence: 99%

A Prognostic Signature Constructed by CTHRC1 and LRFN4 in Stomach Adenocarcinoma

et al. 2021

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BackgroundStomach adenocarcinoma (STAD) is the most common histological type of stomach cancer, which causes a considerable number of deaths worldwide. This study aimed to identify its potential biomarkers with the notion of revealing the underlying molecular mechanisms.MethodsGene expression profile microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The “limma” R package was used to screen the differentially expressed genes (DEGs) between STAD and matched normal tissues. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for function enrichment analyses of DEGs. The STAD dataset from The Cancer Genome Atlas (TCGA) database was used to identify a prognostic gene signature, which was verified in another STAD dataset from the GEO database. CIBERSORT algorithm was used to characterize the 22 human immune cell compositions. The expression of LRFN4 and CTHRC1 in tissues was determined by quantitative real-time PCR from the patients recruited to the present study.ResultsThree public datasets including 90 STAD patients and 43 healthy controls were analyzed, from which 44 genes were differentially expressed in all three datasets. These genes were implicated in biological processes including cell adhesion, wound healing, and extracellular matrix organization. Five out of 44 genes showed significant survival differences. Among them, CTHRC1 and LRFN4 were selected for construction of prognostic signature by univariate Cox regression and stepwise multivariate Cox regression in the TCGA-STAD dataset. The fidelity of the signature was evaluated in another independent dataset and showed a good classification effect. The infiltration levels of multiple immune cells between high-risk and low-risk groups had significant differences, as well as two immune checkpoints. TIM-3 and PD-L2 were highly correlated with the risk score. Multiple signaling pathways differed between the two groups of patients. At the same time, the expression level of LRFN4 and CTHRC1 in tissues analyzed by quantitative real-time PCR were consistent with the in silico findings.ConclusionThe present study constructed the prognostic signature by expression of CTHRC1 and LRFN4 for the first time via comprehensive bioinformatics analysis, which provided the potential therapeutic targets of STAD for clinical treatment.

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CTHRC1 overexpression promotes cervical carcinoma progression by activating the Wnt/PCP signaling pathway

Cited by 19 publications

References 26 publications

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

Leptin Is Associated with Poor Clinical Outcomes and Promotes Clear Cell Renal Cell Carcinoma Progression

A Prognostic Signature Constructed by CTHRC1 and LRFN4 in Stomach Adenocarcinoma

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